| 1. |
- Burstein, R., et al.
(författare)
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Mapping 123 million neonatal, infant and child deaths between 2000 and 2017
- 2019
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 574:7778, s. 353-358
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Tidskriftsartikel (refereegranskat)abstract
- Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2—to end preventable child deaths by 2030—we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000–2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations. © 2019, The Author(s).
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| 2. |
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| 3. |
- Abbafati, Cristiana, et al.
(författare)
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- 2020
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Tidskriftsartikel (refereegranskat)
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| 4. |
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| 5. |
- Kinyoki, DK, et al.
(författare)
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Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017
- 2020
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Ingår i: Nature medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 26:5, s. 750-759
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Tidskriftsartikel (refereegranskat)abstract
- A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic.
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| 6. |
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| 7. |
- Feigin, Valery L., et al.
(författare)
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Global, regional, and national burden of neurological disorders, 1990–2016 : a systematic analysis for the Global Burden of Disease Study 2016
- 2019
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Ingår i: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 18:5, s. 459-480
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Tidskriftsartikel (refereegranskat)abstract
- Background: Neurological disorders are increasingly recognised as major causes of death and disability worldwide. The aim of this analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 is to provide the most comprehensive and up-to-date estimates of the global, regional, and national burden from neurological disorders.Methods: We estimated prevalence, incidence, deaths, and disability-adjusted life-years (DALYs; the sum of years of life lost [YLLs] and years lived with disability [YLDs]) by age and sex for 15 neurological disorder categories (tetanus, meningitis, encephalitis, stroke, brain and other CNS cancers, traumatic brain injury, spinal cord injury, Alzheimer's disease and other dementias, Parkinson's disease, multiple sclerosis, motor neuron diseases, idiopathic epilepsy, migraine, tension-type headache, and a residual category for other less common neurological disorders) in 195 countries from 1990 to 2016. DisMod-MR 2.1, a Bayesian meta-regression tool, was the main method of estimation of prevalence and incidence, and the Cause of Death Ensemble model (CODEm) was used for mortality estimation. We quantified the contribution of 84 risks and combinations of risk to the disease estimates for the 15 neurological disorder categories using the GBD comparative risk assessment approach.Findings: Globally, in 2016, neurological disorders were the leading cause of DALYs (276 million [95% UI 247–308]) and second leading cause of deaths (9·0 million [8·8–9·4]). The absolute number of deaths and DALYs from all neurological disorders combined increased (deaths by 39% [34–44] and DALYs by 15% [9–21]) whereas their age-standardised rates decreased (deaths by 28% [26–30] and DALYs by 27% [24–31]) between 1990 and 2016. The only neurological disorders that had a decrease in rates and absolute numbers of deaths and DALYs were tetanus, meningitis, and encephalitis. The four largest contributors of neurological DALYs were stroke (42·2% [38·6–46·1]), migraine (16·3% [11·7–20·8]), Alzheimer's and other dementias (10·4% [9·0–12·1]), and meningitis (7·9% [6·6–10·4]). For the combined neurological disorders, age-standardised DALY rates were significantly higher in males than in females (male-to-female ratio 1·12 [1·05–1·20]), but migraine, multiple sclerosis, and tension-type headache were more common and caused more burden in females, with male-to-female ratios of less than 0·7. The 84 risks quantified in GBD explain less than 10% of neurological disorder DALY burdens, except stroke, for which 88·8% (86·5–90·9) of DALYs are attributable to risk factors, and to a lesser extent Alzheimer's disease and other dementias (22·3% [11·8–35·1] of DALYs are risk attributable) and idiopathic epilepsy (14·1% [10·8–17·5] of DALYs are risk attributable).Interpretation: Globally, the burden of neurological disorders, as measured by the absolute number of DALYs, continues to increase. As populations are growing and ageing, and the prevalence of major disabling neurological disorders steeply increases with age, governments will face increasing demand for treatment, rehabilitation, and support services for neurological disorders. The scarcity of established modifiable risks for most of the neurological burden demonstrates that new knowledge is required to develop effective prevention and treatment strategies.Funding: Bill & Melinda Gates Foundation.
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| 8. |
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| 9. |
- Sbarra, AN, et al.
(författare)
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Mapping routine measles vaccination in low- and middle-income countries
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 589:7842, s. 415-
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Tidskriftsartikel (refereegranskat)abstract
- The safe, highly effective measles vaccine has been recommended globally since 1974, yet in 2017 there were more than 17 million cases of measles and 83,400 deaths in children under 5 years old, and more than 99% of both occurred in low- and middle-income countries (LMICs)1–4. Globally comparable, annual, local estimates of routine first-dose measles-containing vaccine (MCV1) coverage are critical for understanding geographically precise immunity patterns, progress towards the targets of the Global Vaccine Action Plan (GVAP), and high-risk areas amid disruptions to vaccination programmes caused by coronavirus disease 2019 (COVID-19)5–8. Here we generated annual estimates of routine childhood MCV1 coverage at 5 × 5-km2pixel and second administrative levels from 2000 to 2019 in 101 LMICs, quantified geographical inequality and assessed vaccination status by geographical remoteness. After widespread MCV1 gains from 2000 to 2010, coverage regressed in more than half of the districts between 2010 and 2019, leaving many LMICs far from the GVAP goal of 80% coverage in all districts by 2019. MCV1 coverage was lower in rural than in urban locations, although a larger proportion of unvaccinated children overall lived in urban locations; strategies to provide essential vaccination services should address both geographical contexts. These results provide a tool for decision-makers to strengthen routine MCV1 immunization programmes and provide equitable disease protection for all children.
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| 10. |
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| 11. |
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| 12. |
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| 13. |
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| 14. |
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| 15. |
- Feigin, Valery L., et al.
(författare)
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Global, regional, and national burden of stroke and its risk factors, 1990-2019 : a systematic analysis for the Global Burden of Disease Study 2019
- 2021
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Ingår i: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 20:10, s. 795-820
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Tidskriftsartikel (refereegranskat)abstract
- Background Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings In 2019, there were 12.2 million (95% UI 11.0-13.6) incident cases of stroke, 101 million (93.2-111) prevalent cases of stroke, 143 million (133-153) DALYs due to stroke, and 6.55 million (6.00-7.02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11.6% [10.8-12.2] of total deaths) and the third-leading cause of death and disability combined (5.7% [5.1-6.2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70.0% (67.0-73.0), prevalent strokes increased by 85.0% (83.0-88.0), deaths from stroke increased by 43.0% (31.0-55.0), and DALYs due to stroke increased by 32.0% (22.0-42.0). During the same period, age-standardised rates of stroke incidence decreased by 17.0% (15.0-18.0), mortality decreased by 36.0% (31.0-42.0), prevalence decreased by 6.0% (5.0-7.0), and DALYs decreased by 36.0% (31.0-42.0). However, among people younger than 70 years, prevalence rates increased by 22.0% (21.0-24.0) and incidence rates increased by 15.0% (12.0-18.0). In 2019, the age-standardised stroke-related mortality rate was 3.6 (3.5-3.8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3.7 (3.5-3.9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62.4% of all incident strokes in 2019 (7.63 million [6.57-8.96]), while intracerebral haemorrhage constituted 27.9% (3.41 million [2.97-3.91]) and subarachnoid haemorrhage constituted 9.7% (1.18 million [1.01-1.39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79.6 million [67.7-90.8] DALYs or 55.5% [48.2-62.0] of total stroke DALYs), high body-mass index (34.9 million [22.3-48.6] DALYs or 24.3% [15.7-33.2]), high fasting plasma glucose (28.9 million [19.8-41.5] DALYs or 20.2% [13.8-29.1]), ambient particulate matter pollution (28.7 million [23.4-33.4] DALYs or 20.1% [16.6-23.0]), and smoking (25.3 million [22.6-28.2] DALYs or 17.6% [16.4-19.0]). Interpretation The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries.
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| 16. |
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| 17. |
- Coman, Vasile, et al.
(författare)
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A membrane-, mediator-, cofactor-less glucose/oxygen biofuel cell.
- 2008
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Ingår i: Physical Chemistry Chemical Physics. - : Royal Society of Chemistry (RSC). - 1463-9084 .- 1463-9076. ; 10:40, s. 6093-6096
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Tidskriftsartikel (refereegranskat)abstract
- We report the fabrication and characterisation of a non-compartmentalised, mediator and cofactor free glucose-oxygen biofuel cell based on adsorbed enzymes exhibiting direct bioelectrocatalysis, viz. cellobiose dehydrogenase from Dichomera saubinetii and laccase from Trametes hirsuta as the anodic and cathodic bioelements, respectively, with the following characteristics: an open-circuit voltage of 0.73 V; a maximum power density of 5 muW cm(-2) at 0.5 V of the cell voltage and an estimated half-life of >38 h in air-saturated 0.1 M citrate-phosphate buffer, pH 4.5 containing 5 mM glucose.
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| 18. |
- Figueiredo, Carina, et al.
(författare)
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Effect of Protection Polymer Coatings on the Performance of an Amperometric Galactose Biosensor in Human Plasma
- 2024
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Ingår i: Biosensors. - 2079-6374. ; 14:4
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Tidskriftsartikel (refereegranskat)abstract
- Galactose monitoring in individuals allows the prevention of harsh health conditions related to hereditary metabolic diseases like galactosemia. Current methods of galactose detection need development to obtain cheaper, more reliable, and more specific sensors. Enzyme-containing amperometric sensors based on galactose oxidase activity are a promising approach, which can be enhanced by means of their inclusion in a redox polymer coating. This strategy simultaneously allows the immobilization of the biocatalyst to the electroactive surface and hosts the electron shuttling units. An additional deposition of capping polymers prevents external interferences like ascorbic or uric acid as well as biofouling when measuring in physiological fuels. This work studies the protection effect of poly(2-methacryloyloxyethyl phosphorylcholine-co-glycidyl methacrylate (MPC) and polyvinylimidazole-polysulfostyrene (P(VI-SS)) when incorporated in the biosensor design for the detection of galactose in human plasma.
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| 19. |
- Gonzalez-Arribas, Elena, et al.
(författare)
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Transparent, mediator- and membrane-free enzymatic fuel cell based on nanostructured chemically modified indium tin oxide electrodes
- 2017
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Ingår i: Biosensors & bioelectronics. - : Elsevier. - 0956-5663 .- 1873-4235. ; 97, s. 46-52
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Tidskriftsartikel (refereegranskat)abstract
- We detail a mediator- and membrane-free enzymatic glucose/oxygen biofuel cell based on transparent and nanostructured conducting supports. Chemically modified indium tin oxide nanoparticle modified electrodes were used to substantially increase the active surface area without significantly compromising transparency. Two different procedures for surface nanostructuring were employed, viz. spray-coating and drop-coating. The spray-coated biodevice showed superior characteristics as compared to the drop-coated enzymatic fuel cell, as a result of the higher nanostructured surface area as confirmed by electrochemical characterisation, as well as scanning electron and atomic force microscopy. Subsequent chemical modification with silanes, followed by the immobilisation of either cellobiose dehydrogenase from Corynascus thermophiles or bilirubin oxidase from Myrothecium verrucaria, were performed to obtain the bioanodes and biocathodes, respectively. The optimised biodevice exhibited an OCV of 0.67 V and power output of up to 1.4 mu W/cm(2) at an operating voltage of 0.35 V. This is considered a significant step forward in the field of glucose/oxygen membrane- and mediator-free, transparent enzymatic fuel cells.
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| 20. |
- Gutierrez-Sanchez, Cristina, et al.
(författare)
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Third-generation oxygen amperometric biosensor based on Trametes hirsuta laccase covalently bound to graphite electrode
- 2015
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Ingår i: Chemické zvesti. - : Slovak Academic Press. - 0366-6352 .- 1336-9075. ; 69:1, s. 237-240
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Tidskriftsartikel (refereegranskat)abstract
- The response of low-density graphite electrodes hosting Trametes hirsuta laccase in a direct electron transfer regime is presented for real-time analysis of O2 concentrations. The use of contrasting immobilisation methods developed for biocathodes affords good reproducibility and reliability of the amperometric biosensor, which shows a limit of detection below 1 µM and a sensitivity slightly higher than 60 nA cm−2 M.
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| 21. |
- Haberska, Karolina, et al.
(författare)
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Direct electron transfer reactions between human ceruloplasmin and electrodes.
- 2009
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Ingår i: Bioelectrochemistry. - : Elsevier BV. - 1878-562X .- 1567-5394. ; 76, s. 34-41
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Tidskriftsartikel (refereegranskat)abstract
- In an effort to find conditions favouring bioelectrocatalytic reduction of oxygen by surface-immobilised human ceruloplasmin (Cp), direct electron transfer (DET) reactions between Cp and an extended range of surfaces were considered. Exploiting advances in surface nanotechnology, bare and carbon-nanotube-modified spectrographic graphite electrodes as well as bare, thiol- and gold-nanoparticle-modified gold electrodes were considered, and ellipsometry provided clues as to the amount and form of adsorbed Cp. DET was studied under different conditions by cyclic voltammetry and chronoamperometry. Two Faradaic processes with midpoint potentials of about 400 mV and 700 mV vs. NHE, corresponding to the redox transformation of copper sites of Cp, were clearly observed. In spite of the significant amount of Cp adsorbed on the electrode surfaces, as well as the quite fast DET reactions between the redox enzyme and electrodes, bioelectrocatalytic reduction of oxygen by immobilised Cp was never registered. The bioelectrocatalytic inertness of this complex multi-functional redox enzyme interacting with a variety of surfaces might be associated with a very complex mechanism of intramolecular electron transfer involving a kinetic trapping behaviour.
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| 22. |
- Jarne, Carmen, et al.
(författare)
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Underpotential Photoelectrooxidation of Water by SnS2-Laccase Co-catalysts on Nanostructured Electrodes with Only Visible-Light Irradiation
- 2019
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Ingår i: ChemElectroChem. - : John Wiley & Sons. - 2196-0216. ; 6:10, s. 2755-2761
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Tidskriftsartikel (refereegranskat)abstract
- More sustainable ways to produce and store energy are urgently needed to reduce our dependence on fossil fuels, which are the principal drivers of global warming and pollution. Hydrogen may become the energy vector needed for this purpose if its production through water splitting can become competitive against steam methane reforming. Even after decades of research, the proposed strategies for water splitting are not efficient enough to overcome the high overpotential of the water oxidation reaction. In a quest for new approaches to this problem, recent studies have attempted to combine inorganic catalysts with biocatalysts, aiming to open new possibilities towards a definitive solution. In the present work we have tested a chalcogenide semiconductor, SnS2, characterized by a deep valence band and a visible-light band gap of approximately 2.2eV (lambda=550nm). Preparation of a fluorine-doped tin oxide electrode modified with SnS2 and laccase allowed water oxidation at a lower overpotential, taking better advantage of light energy. Additionally, indium tin oxide nanoparticles were added to increase the contact area between SnS2 and the electrode surface and thereby improve charge separation for photobioelectrocatalytic water oxidation. We tested the nanostructured anode electrodes under different applied potentials and irradiance intensities from a solar simulator to find the optimal photonic and faradaic efficiencies.
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| 23. |
- Ressine, Anton, et al.
(författare)
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Bioelectrochemical studies of azurin and laccase confined in three-dimensional chips based on gold-modified nano-/microstructured silicon
- 2010
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Ingår i: Biosensors & Bioelectronics. - : Elsevier BV. - 1873-4235 .- 0956-5663. ; 25:5, s. 1001-1007
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Tidskriftsartikel (refereegranskat)abstract
- Double-sided three-dimensional porous silicon chips, 6 mm x 6 mm, covered with a 40 nm gold (nano)layer, were fabricated from a porous silicon wafer. Scanning electron microscopy along with electrochemical characterisation showed sample conductivity, mechanical stability, and high surface area of the thus fabricated devices, viz. 10 times higher electrochemically active surface area compared to the geometric area. The three-dimensional gold coated silicon chips were further modified with thiol layers, followed by immobilisation of a simple copper-containing redox protein, azurin, or a complex multicopper redox enzyme, laccase. The bioelectrochemical studies showed very high surface concentrations of azurin and laccase, i.e. close to the theoretical monolayer coverage. However, direct electron transfer reactions between the biomolecules and gold surfaces were observed only for a small percentage of the immobilised redox protein and enzyme, respectively. Thus, highly efficient oxygen-bioelectroreduction on laccase-modified 3D thiol-gold-porous silicon chips (as compared to planar laccase-modified gold electrodes, 42 mu A/cm(2) vs. 7 mu A/cm(2), respectively) was obtained only in the presence of an efficient soluble redox mediator. (C) 2009 Elsevier B.V. All rights reserved.
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| 24. |
- Tapia, Cristina, et al.
(författare)
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Lactase-Catalyzed Bioelectrochemical Oxidation of Water Assisted with Visible Light
- 2017
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Ingår i: ACS Catalysis. - : American Chemical Society (ACS). - 2155-5435. ; 7:7, s. 4881-4889
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Tidskriftsartikel (refereegranskat)abstract
- Here we present the modification of fluorinated tin oxide electrodes with In2S3, an n-type semiconductor chalcogenide that absorbs visible light (lambda <= 600 nm), and its further use as an active scaffold for laccase-catalyzed oxidation of water. Illumination of an FTO-In2S3-laccase electrode yields O-2 production at much lower applied potential in comparison to the previous example using the same laccase, where only electric energy was applied. The present system allows a diversification of the energy applied to accomplish the water splitting, taking a portion of it from the sun. This work is the first example where an enzyme other than PSII has been used in combination with visible light to biocatalyze O-2 evolution.
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| 25. |
- Tapia, Cristina, et al.
(författare)
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Wiring of Photosystem I and Hydrogenase on an Electrode for Photoelectrochemical H2 Production by using Redox Polymers for Relatively Positive Onset Potential
- 2017
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Ingår i: ChemElectroChem. - : Wiley. - 2196-0216. ; 4:1, s. 90-95
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Tidskriftsartikel (refereegranskat)abstract
- Photosystem I (PSI) is combined with Desulfovibrio gigas hydrogenase for the bioelectrocatalytic photosynthesis of hydrogen at an electrode surface. The activity of these two biocatalysts is linked by two redox polymers; a redox polymer with a relatively positive potential (loaded with an Os complex) is able to reduce PSI and thus facilitates the production of photoexcited electrons, whereas redox polymers of relatively low potential are able to transfer electrons to the hydrogenase. Two negative-potential redox polymers are tested, with either a viologen pendant (4-methyl-4′-bromopropylviologen functionalized linear polyethylenimine) or a cobaltocene pendant (cobaltocene-functionalized branched polyethylenimine, Cc-BPEI). Both are able to protect hydrogenase from O2 inactivation, but only the use of Cc-BPEI yields significant photocurrents for H+ reduction, likely due to its lower redox potential. The photocurrents obtained are found to be proportional to the quantity of H2 produced, reaching a maximum of −30 μA cm−2 for the system incorporating Cc-BPEI and showing a relatively positive onset potential at +0.38 V versus SHE.
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| 26. |
- W A Koedam, Thomas, et al.
(författare)
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Oncological Outcomes After Anastomotic Leakage After Surgery for Colon or Rectal Cancer: Increased Risk of Local Recurrence
- 2020
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Ingår i: National Center for Biotechnology information.
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to evaluate oncological outcome for patients with and without anastomotic leakage after colon or rectal cancer surgery. Summary of background data: The role of anastomotic leakage in oncological outcome after colorectal cancer surgery is still topic of debate and impact on follow-up and consideration for further treatment remains unclear. Methods: Patients included in the international, multicenter, non-inferior, open label, randomized, controlled trials COLOR and COLOR II, comparing laparoscopic surgery for curable colon (COLOR) and rectal (COLOR II) cancer with open surgery, were analyzed. Patients operated by abdominoperineal excision were excluded. Both univariate and multivariate analyses were performed to investigate the impact of leakage on overall survival, disease-free survival, local and distant recurrences, adjusted for possible confounders. Primary endpoints in the COLOR and COLOR II trial were disease-free survival and local recurrence at 3-year follow-up, respectively, and secondary endpoints included anastomotic leakage rate. Results: For colon cancer, anastomotic leakage was not associated with increased percentage of local recurrence or decreased disease-free-survival. For rectal cancer, an increase of local recurrences (13.3% vs 4.6%; hazard ratio 2.96; 95% confidence interval 1.38-6.34; P = 0.005) and a decrease of disease-free survival (53.6% vs 70.9%; hazard ratio 1.67; 95% confidence interval 1.16-2.41; P = 0.006) at 5-year follow-up were found in patients with anastomotic leakage. Conclusion: Short-term morbidity, mortality, and long-term oncological outcomes are negatively influenced by the occurrence of anastomotic leakage after rectal cancer surgery. For colon cancer, no significant effect was observed; however, due to low power, no conclusions on the influence of anastomotic leakage on outcomes after colon surgery could be reached. Clinical awareness of increased risk of local recurrence after anastomotic leakage throughout the follow-up is mandatory. Trial registration: Registered with ClinicalTrials.gov, number NCT00387842 and NCT00297791.
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